Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation in mesenteric arteries from streptozotocin-induced diabetic mice
Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation in mesenteric arteries from streptozotocin-induced diabetic mice
复制标题
DOI：
10.1016/j.vph.2006.02.007
复制
发表时间：
2006-06-01
影响因子：
4
通讯作者：
Kamata, Katsuo
中科院分区：
文献类型：
--
作者：
Matsumoto, Takayuki;Miyamori, Kiyoto;Kamata, Katsuo
我们假设，由内皮衍生的超极化因子（EDHF）的贡献乙酰胆碱（ACh）诱导的内皮依赖性舒张（EDR）可能会改变肠系膜动脉链脲佐菌素（STZ）诱导的糖尿病小鼠。在内皮完整的制剂中，乙酰胆碱诱导的EDR（但不是硝普钠诱导的舒张）在STZ组比年龄匹配的对照组弱。吲哚美辛（10 μ M）在两组中对EDR均无显著影响，表明环氧合酶产物，包括前列环素，不涉及。STZ组的吲哚美辛耐药EDR较对照组弱。为了分离EDR的EDHF抗性组分，在整个下一个实验中，在浴溶液中存在Charybdotoxin（100 nM）和apamin（100 nM）。这种抗EDHF的松弛在两组之间没有显著差异。另一方面，EDHF介导的松弛显着弱于STZ组比对照组，并完全阻断溶血磷脂酰胆碱（LPC，10 μ M）在每个组。两组eNOS蛋白表达相似。这些结果表明，（a）1型糖尿病小鼠肠系膜动脉中存在的内皮功能障碍主要归因于EDHF信号转导的减少，（B）LPC可能参与EDHF介导的舒张的衰减。(c)2006爱思唯尔公司All rights reserved.
We hypothesized that the contribution made by endothelium-derived hyperpolarizing factor (EDHF) to acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) might be altered in mesenteric arteries from streptozotocin (STZ)-induced diabetic mice. In endothelium-intact preparations, the ACh-induced EDR (but not the sodium nitroprusside-induced relaxation) was weaker in the STZ group than in age-matched controls. Indomethacin (10 mu M) had no significant effect on EDR in either group, indicating that cyclooxygenase products, including prostacyclin, are not involved. This indomethacin-resistant EDR was weaker in the STZ group than in the controls. To isolate the EDHF-resistant component of EDR, charybdotoxin (100 nM) and apamin (100 nM) were present in the bath solution throughout the next experiment. This EDHF-resistant relaxation did not differ significantly between the two groups. On the other hand, the EDHF-mediated relaxation was significantly weaker in the STZ group than in the controls, and it was completely blocked by lysophosphatidylcholine (LPC, 10 mu M) in each group. The eNOS protein expression was similar between the two groups. These results suggest that (a) the endothelial dysfunction present in mesenteric arteries from type 1 diabetic mice is largely attributable to reduced EDHF signaling, and (b) LPC may be involved in this attenuation of EDHF-mediated relaxation. (c) 2006 Elsevier Inc. All rights reserved.